Testing the Safety and Feasibility of Immunotherapy Drugs, Botensilimab and Balstilimab, Before Surgery for Clear Cell Renal Cell Carcinoma, NEO RoBOT Trial

NCT07516366 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2026-0219410743UM1CA186689
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests the effect of botensilimab and balstilimab before surgery (neoadjuvant) in treating patients with high-risk clear cell renal cell cancer that has not spread from where it first started to other areas of the body (non-metastatic). The current standard treatment for patients with non-metastatic clear cell renal cell cancer may include surgery to completely remove the tumor. This typically involves removing the kidney or part of the kidney (nephrectomy). Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving neoadjuvant botensilimab and balstilimab may be safe, tolerable, and/or effective in treating patients with high-risk non-metastatic clear cell renal cell cancer before undergoing a nephrectomy.

Conditions

Stage II Renal Cell Cancer AJCC v8; Stage III Renal Cell Cancer AJCC v8; Clear Cell Renal Cell Carcinoma; Stage IV Renal Cell Cancer AJCC v8

Outcome Measures

Primary Outcomes (3)

• Proportion of patients successfully completing neoadjuvant treatment and undergoing planned definitive surgical resection of primary tumor (radical or partial nephrectomy) without significant treatment related delays

  The intervention will be considered feasible if at least 80% of enrolled patients (13 out of 16) successfully undergo planned radical or partial nephrectomy following treatment.

  Up to 1 year post-surgery

• Incidence and severity of treatment-related adverse events

  Will be analyzed descriptively using frequencies and proportions, stratified by severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

  Up to 30 days after last dose of study treatment

• Incidence and severity of surgical complications

  Will be summarized using the Clavien-Dindo Classification.

  Up to 30 days after surgery

Secondary Outcomes (6)

• Objective response rate (ORR)

  After neoadjuvant treatment, assessed up to 1 year post-nephrectomy

• Major pathologic response (MPR) rate

  Up to 1 year post-surgery

• Partial pathologic rate (PPR) rate

  Up to 1 year post-surgery

• Rates of distant metastasis

  Up to 1 year post-surgery

• Rates of local recurrence

  Up to 1 year post-surgery

Other Outcomes (6)

• Changes in immune biomarkers

  At baseline and after treatment, assessed up to 1 year

• Systemic immune activation markers

  At baseline and after treatment, assessed up to 1 year

• T-cell clonality and diversity

  At pre and post treatment, assessed up to 1 year

Study Arms (1)

Treatment (botensilimab, balstilimab)

EXPERIMENTAL

Patients receive botensilimab IV over 30 minutes on day 1 of weeks 1 and 7 and balstilimab IV over 30 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity. Patients undergo nephrectomy 12-16 weeks from the initiation of neoadjuvant therapy. Additionally, patients undergo blood sample collection and CT throughout the study.

Biological: Balstilimab; Procedure: Biospecimen Collection; Biological: Botensilimab; Procedure: Computed Tomography; Procedure: Nephrectomy; Other: Questionnaire Administration

Interventions

Botensilimab BIOLOGICAL

Given IV

Also known as: AGEN 1181, AGEN-1181, AGEN1181, Anti-CTLA-4 Monoclonal Antibody AGEN1181

Treatment (botensilimab, balstilimab)

Nephrectomy PROCEDURE

Undergo nephrectomy

Treatment (botensilimab, balstilimab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (botensilimab, balstilimab)

Balstilimab BIOLOGICAL

Given IV

Also known as: AGEN 2034, AGEN-2034, AGEN2034

Treatment (botensilimab, balstilimab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (botensilimab, balstilimab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (botensilimab, balstilimab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have biopsy-confirmed, non-metastatic, high-risk renal cell carcinoma (RCC) with a clear cell component, defined as clinical stage T2N0, T3N0, T4N0, or any T stage with N1 disease (i.e., T2a-T4NanyM0 or TanyN1M0), and no evidence of metastatic disease
• Participants with resectable RCC are eligible, including those who have previously undergone surgical resection for RCC and subsequently developed resectable recurrent disease. Patients must be candidates for further curative-intent surgical resection. Prior systemic therapy for RCC (including VEGF-targeted therapy, immune checkpoint inhibitors, HIF-2α inhibitors, or other systemic anticancer therapies) is not allowed
• Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of botensilimab in combination with balstilimab in patients \< 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky ≥ 60%)
• Patients must be considered suitable for curative-intent surgical resection of RCC, including radical or partial nephrectomy, as determined by the urology team and the treating physician according to standard clinical guidelines
• Absolute neutrophil count ≥ 1,000/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN
• Glomerular filtration rate (GFR) 50 mL/min (calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Also including a prior history of renal cell carcinoma
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better

You may not qualify if:

• Patients who have suspected or proven metastatic renal cell carcinoma
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to botensilimab or balstilimab
• Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
• Pregnant women are excluded from this study because botensilimab and balstilimab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with botensilimab or balstilimab, breastfeeding should be discontinued if the mother is treated with botensilimab or balstilimab
• Patients without a clear cell component in their baseline kidney biopsy or non-clear cell renal cell carcinoma (RCC) are excluded from this study
• Patients who have received prior treatment with an anti-PD-1, anti-programmed cell death protein ligand 1 (PD-L1), anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Patients who have undergone major surgery within 28 days prior to the start of the study
• Patients with any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\> 10 mg daily prednisone equivalent) or immunosuppressive medications within 14 days prior to first dose of study drug; the exception would be for syndromes which would not be expected to recur in the absence of an external trigger. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Patients with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
• Patients with a baseline corrected QT interval (Fridericia's corrected QT interval \[QTcF\]) \> 480 ms on screening electrocardiogram (ECG), a history of congenital long QT syndrome, or clinically significant cardiac arrhythmias will be excluded

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Yale University Cancer Center LAO

New Haven, Connecticut, 06520, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

balstilimab; Specimen Handling; Nephrectomy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Adanma Anji Ayanambakkam Attanathi

  Yale University Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 8, 2026
• Study Start (Estimated): May 17, 2027
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 14, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)